Deregulation of oxyradical metabolism, as reflected in abnormal erythrocyte activities of three critical enzymes of the antioxidant defence system (superoxide dismutase, glutathione peroxidase, and catalase) has been reported in schizophrenic patients. The pathophysiological significance, if any, of these findings has not been investigated systematically. In a preliminary study, we found in erythrocytes significantly increased superoxide dismutase activity, but decreased catalase activity, and a nonsignificantly increased glutathione peroxidase activity, in schizophrenic patients, relative to normal controls. The known physiology of oxyradical metabolism suggests that these enzymes act cooperatively, and that alterations in the activity of one enzyme without compensatory response in other enzymes may increase the potential for cellular dysfunction and damage. No previously reported study has examined all three enzymes simultaneously in schizophrenic patients. We propose to examine the diagnostic specificity of abnormal of activities of the three enzymes in 30 schizophrenic patients, 30 bipolar patients (psychiatric control group), and 30 normal controls. More critically, we will compare the patterns of alterations in these enzymes across the diagnostic groups, using multivariate statistical methods. Abnormal oxyradical metabolism has also been implicated in the pathogenesis of tardive dyskinesia (TD). We will examine the relations of the patterns and activities of these enzyme to TD in both schizophrenic and bipolar patients. TD will be examined both as a categorical measure (TD vs non-TD), and as a continuous measure of severity considering separately discrete topographical distributions of dyskinetic movements. Half of each diagnostic group will comprise patients with TD, and the TD and non-TD groups will be matched for mean age and distribution of Sex. Finally, we will examine neuroleptics effects on erythrocyte activities of antioxidant defence system enzymes in schizophrenic patients using a within-subject, on-off neuroleptic design, and in bipolar patients, using a similar design during a six-month prospective follow up study.